What are other Names for this Test? (Equivalent Terms)
- Gene Mutation Analysis for Restrictive Cardiomyopathy
- Molecular Testing for RCM
- Test for Molecular Diagnosis of Restrictive Cardiomyopathy
What is Molecular Testing for Restrictive Cardiomyopathy? (Background Information)
- Molecular Testing for Restrictive Cardiomyopathy is a genetic test that is helpful in aiding a diagnosis of the disorder. The lab test results may also be subsequently useful in taking appropriate treatment decisions
- Restrictive cardiomyopathy (RCM) is the most infrequent of the known cardiomyopathies. The condition can occur in individuals of any age. Cardiomyopathy is a term used for a variety of conditions that affect the muscles of the heart
- The onset of RCM can vary; it can occur at any age. In children with the condition, the age of onset is typically 5-6 years, and young girls appear more prone to it than boys. The disorder can affect all populations (racial and ethnic groups)
- The signs and symptoms of restrictive cardiomyopathy include shortness of breath during exertion or while resting, fainting, fatigue, chest pain, and irregular heartbeats. Children with the congenital form of RCM may not grow or gain weight normally
Mutation(s) in the TNNI3 gene are known to cause the inherited form of restrictive cardiomyopathy.
- This gene codes for troponin I protein, which, when mutated, does not allow the heart muscles to relax completely
- The mutation is inherited in an autosomal dominant pattern, in which a single defective copy of the gene in each cell of the individual is sufficient to cause RCM
- Molecular testing may be required for discerning the gene mutation(s) in some cases of restrictive cardiomyopathy
A positive or negative test result should always be interpreted in the context of the individual’s overall signs and symptoms.
Molecular testing, in general, can be performed using a variety of methods. Some of these methods include:
- In situ hybridization techniques, such as fluorescence in situ hybridization (FISH)
- Immunohistochemistry (IHC)
- Next-generation sequencing (NGS)
- Methylation profiling
- Polymerase chain reaction (PCR)
- Comparative genomic hybridization (CGH)
- Karyotyping including spectral karyotyping
- mRNA analysis
- Tissue microarrays (TMAs)
- Southern blot test
- Northern blot test
- Western blot test
- Eastern blot test
The methodology used for restrictive cardiomyopathy may vary from one laboratory to another.
Note: Molecular testing has limitations depending on the method being used, and genetic mutational abnormalities being tested. This can affect the results on a case-by-case basis. Consultation with your healthcare provider will help in determining the right test and right molecular method, based on individual circumstances.
What are the Clinical Indications for performing the Molecular Testing for Restrictive Cardiomyopathy Test?
Molecular Testing for Restrictive Cardiomyopathy may be undertaken in the following situations:
- To assist (and in some cases, confirm) the initial diagnosis of restrictive cardiomyopathy
- To check for or ascertain a family history of the disorder
- To distinguish other conditions that have similar features (signs and symptoms)
- To help determine treatment options
How is the Specimen Collected for Molecular Testing for Restrictive Cardiomyopathy?
The type and source and specimen sample requirements will depend on the preference of the individuals and the preference of the testing lab. Thus, it may vary from one individual to another and from one lab to another. Therefore, it is important to contact the testing lab for exact specimen requirements, before initiating the collecting and testing process.
Following is the specimen collection process for Molecular Testing for Restrictive Cardiomyopathy:
- Sample on which the test is performed may include:
- Peripheral blood in individuals showing signs and symptoms suspected of RCM
- Bone marrow biopsy specimen
- For mitochondrial DNA testing, usually a muscle biopsy or a liver biopsy is preferred
- In case of expectant mothers, prenatal testing through amniotic fluid and chorionic villi sampling
- Fetal cord blood
- Fresh tissue from biopsy
- Fresh tissue from autopsy sample
- Fresh tissue from fetal demise
- Buccal brushes: Using the kit that is provided by the testing laboratory, buccal brushes can be used to collect the specimen, by scraping the inner cheek lining (buccal mucosa)
- Oral rinse specimens
- Body fluids such as saliva, tears, and semen
- Dried blood spots: This specimen type is usually requested in situations where the collection and/or shipping of whole blood is not practical
- In some cases, hair samples (with attached roots), finger nails, and buccal swabs, may be acceptable
- Formalin-fixed paraffin-embedded solid tumor tissue (FFPE tumor tissue), often referred to as paraffin block of the tumor
- Products of conception sample from aborted pregnancy
- Process of obtaining the sample: As outlined by the laboratory testing facility
- Preparation required: As outlined by the laboratory testing facility
Limitations of specimen while testing for restrictive cardiomyopathy
- For blood specimens: Individuals, who have received platelet transfusions, red blood transfusion, or white blood (leukocyte) transfusion, should wait at least 4 weeks before providing a blood specimen
- The following specimens may not be acceptable in individuals who have received heterologous bone marrow transplant (in the past):
- Peripheral blood samples
- Oral rinse specimens
- Bone marrow biopsy specimens
- Peripheral blood samples
- Testing for RCM should not be performed on a transplanted organ/specimen, since the genetic material belongs to the donor and not to the individual being tested
- Formalin-fixed paraffin-embedded solid tumor tissue: In many cases, FFPE tissue blocks are usually not acceptable. Please contact the testing lab to ascertain, if it is an acceptable sample specimen
- In some cases, a different source of specimen may be acceptable to the laboratory performing the test
Occasionally, additional samples may be required to either repeat the test or to perform follow-up testing.
Turnaround time for test results
- Depending on the location of testing, it may take from 2 to 8 weeks from the time of sample collection, to obtain the test results
Sample storage information
- Many hospitals preserve the paraffin blocks for at least 7 years
- In general, older paraffin blocks (over 5 years) may affect the detection of specific mutations, due to degradation of the tissue specimen over time
Cost of Molecular Testing for Restrictive Cardiomyopathy:
- The cost of the test procedure depends on a variety of factors, such as the type of your health insurance, annual deductibles, co-pay requirements, whether your healthcare provider/facility is in-network or out-of-network of your insurance company
- In many cases, an estimate may be provided before the test is conducted. The final amount may depend upon the findings during the test procedure and post-operative care, if required
What is the Significance of the Molecular Testing for Restrictive Cardiomyopathy Result?
The significance of Molecular Testing for Restrictive Cardiomyopathy is explained below:
- A positive test result helps aid, and in some cases, confirm the diagnosis of restrictive cardiomyopathy
- The test results can help in the following manner:
- Exclude other conditions presenting with similar signs and symptoms
- Exclude other conditions presenting with similar signs and symptoms
- Determine the prognosis of the patient
- In management of the condition following birth of the child, if the condition is diagnosed prenatally
- In making treatment decisions
- Individuals showing a positive test result during pregnancy may benefit from genetic counseling
- If a causative gene mutation for restrictive cardiomyopathy is identified in a family, then genetic counseling may be recommended to help assess the risk, before planning for a child
The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario.
Additional and Relevant Useful Information:
- Many laboratories may not have the capability to perform this test. Only highly-specialized labs with advanced facilities and testing procedures may offer this test
- Ongoing research may discover additional gene mutations for this condition. This may further contribute towards diagnosis and treatment. Please consult with your healthcare provider for updates
Certain medications may influence the outcome of the test. Hence, it is important to inform your healthcare provider of the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid any possibility of a misdiagnosis.
What are some Useful Resources for Additional Information?
Please visit our Laboratory Procedures Center for more physician-approved health information:
References and Information Sources used for the Article:
https://ghr.nlm.nih.gov/primer/testing/genetictesting (accessed on 03/16/2017)
https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5806a1.htm (accessed on 03/16/2017)
http://www.nature.com/gim/journal/v10/n5/full/gim200852a.html (accessed on 03/16/2017)
http://pediatrics.aappublications.org/content/106/6/1494 (accessed on 03/16/2017)
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/dilated-restrictive-cardiomyopathy/ (accessed on 03/16/2017)
https://genetics.uvahealth.com/cardiomyopathies/restrictive-cardiomyopathy-rcm/restrictive-cardiomyopathy-rcm-screening/ (accessed on 03/16/2017)
Helpful Peer-Reviewed Medical Articles:
Carrano, A. V., et al. Measurement and purification of human chromosomes by flow cytometry and sorting. Proceedings of the National Academy of Sciences 76, 1382–1384 (1979)
Drets, M. E., & Shaw, M. W. Specific banding patterns of human chromosomes. Proceedings of the National Academy of Sciences 68, 2073–2077 (1971)
Druker, B. J. Perspectives on the development of a molecularly targeted agent. Cancer Cell 1, 31–36 (2002)
Parra, I., & Windle, B. High resolution visual mapping of stretched DNA by fluorescent hybridization. Nature Genetics 5, 17–21 (1993) doi:10.1038/ng0993-17
Pinkel, D., et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nature Genetics 20, 207–211 (1998) doi:10.1038/2524
Speicher, M. R., et al. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nature Genetics 12, 368–375 (1996) doi:10.1038/ng0496-368
Hershberger, R. E., Lindenfeld, J., Mestroni, L., Seidman, C. E., Taylor, M. R., & Towbin, J. A. (2009). Genetic evaluation of cardiomyopathy—a Heart Failure Society of America practice guideline. Journal of cardiac failure, 15(2), 83-97.
Kubo, T., Gimeno, J. R., Bahl, A., Steffensen, U., Steffensen, M., Osman, E., ... & McKenna, W. J. (2007). Prevalence, clinical significance, and genetic basis of hypertrophic cardiomyopathy with restrictive phenotype. Journal of the American College of Cardiology, 49(25), 2419-2426.
Caleshu, C., Sakhuja, R., Nussbaum, R. L., Schiller, N. B., Ursell, P. C., Eng, C., ... & Rame, J. E. (2011). Furthering the link between the sarcomere and primary cardiomyopathies: restrictive cardiomyopathy associated with multiple mutations in genes previously associated with hypertrophic or dilated cardiomyopathy. American Journal of Medical Genetics Part A, 155(9), 2229-2235.
Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: March 29, 2017
Last updated: March 29, 2017
Was this article helpful?